Empronium, which has the structural formula ##STR1## is a known therapeutically active substance which mainly is used in the form of its bromide. Its preparation is described e.g. in Chemical Abstracts 48, 729 a (1954). It is used as an anticholinergic and antispasmodic agent, mainly in the treatment of ailments related to the bladder function in man, for example incontinence, urinary frequency, irritable bladder, nervous bladder, and neurogenic bladder.
Doxycycline, which has the structural formula ##STR2## is also a known therapeutically active substance. It is mainly used in the form of its hydrochloride. It is used as an antibiotically active agent in the treatment of bacterial infections.
Also propranolol, which has the structural formula ##STR3## is a known therapeutically active substance. It is mainly used in the form of its hydrochloride. It is used as a betareceptor blocking agent.
The customary mode of administration of emepronium is by the oral route, mostly in the form of tablets which contain emepronium in the form of its bromide together with usual inert tabletting aids such as swelling agents. Patients taking emepronium bromide tablets are advised to swallow them with water. However, since patients suffering from bladder ailments at the same time often are advised to reduce their intake of fluid, there is a risk that the tablets are swallowed with too little water. The tablet may then, when disintegrating during its passage through the oesophagus, stick to the mucosa in the oesophagus whereby high local concentrations of emepronium bromide are created. Emepronium bromide has irritating effect on the mucosa, and such high local concentrations may cause severe irritation and ulceration in the oesophagus. Such effects have been described i.a. by Bennett, Oesophageal ulceration due to emepronium bromide, Lancet 1977, 1, 810. There is also risk for mouth ulcers caused by emepronium bromide.
A further problem with emepronium bromide is that it tastes very bitter. Liquid dose formulations are therefore accepted by the patients only with difficulty.
Also doxycycline and propranolol are mostly administered orally in the form of tablets containing doxycycline hydrochloride and propranolol hydrochloride. Also such tablets tend very easily to stick to the mucosa in the oesophagus giving the same type of irritation and ulceration as tablets containing emepronium bromide.